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The effect of using fibrates in conjunction with statins for the management of dyslipidemia in persons with Type II diabetes mellitus

THE EFFECT OF USING FIBRATES
IN CONJUNCTION WITH STATINS FOR THE MANAGEMENT OF
DYSLIPIDEMIA IN PERSONS WITH TYPE II DIABETES MELLITUS
by
Hae Sun Suh
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(PHARMACEUTICAL ECONOMICS AND POLICY)
August 2009
Copyright 2009 Hae Sun Suh

OBJECTIVES: To examine the effect of a statin plus fibrate combination therapy versus a statin monotherapy on the occurrence of cardiovascular disease (CVD) in subjects with type II diabetes in a managed care setting.; METHODS: “Combo-group” - defined as subjects who used a statin less than six-months and augmented to a statin plus fibrate for more than six-months - and “mono-group” - defined as subjects who used a statin less than six-months and remained on the statin for more than six-months - were identified among subjects with type II diabetes with a two-year intake period (7/1/2002-6/30/2004) and a three-year follow-up using administrative claims from a West-coast based health plan in the US covering a population of four million. Outcomes were identified as any occurrence of CVD which included ischemic heart disease, cerebrovascular disease, and peripheral vascular disease. A univariate probit model was developed to evaluate adjusted CVD-risk. Since this was a retrospective database analysis, we suspected an endogeneity issue in regards to the treatment indicator variable. To control for the potentially endogenous treatment variable, we built a two-stage probit model that used an instrumental variable method using two-stage residual inclusion estimation. We also used the two-stage least squares (two-stage predictor substitution method) model and the bivariate probit model.; We used physician prescribing preference as the instrumental variable. To test the validity of the instrument, we tested for the correlation between the instrument and treatment indicator using a standard t-test. To check whether it is valid to exclude the instrument from the main equation, a Wald test was performed. The Stock and Yogo test was used to check the weak instrument issue. To test the endogeneity of the treatment indicator, we performed a Hausman test.; RESULTS: Mean (±SD) age was 58 (±11) years in the combo-group (N = 318) and 61 (±11) years in the mono-group (N = 9,928). In the combo-group, mean (±SD) treatment-duration was 296 (±347) days for the statin plus fibrate therapy following 118 (±52) days for the statin-monotherapy. In the mono-group, mean (±SD) treatment-duration was 554 (±413) days for the statin-monotherapy following 115 (±51) days for the statin-monotherapy. The proportion of CVD occurrence between groups were not significantly different (combo-group vs. statin mono-group, P = 0.522). Adjusting for age, gender, prior CVD, CVD-related pharmacy-costs, Elixhauser-comorbidity, and diabetes with complication, the combo-group experienced 6.5% less CVD than the mono-group on average (P = 0.009). All covariates were significantly associated with the occurrence of CVD. For the instrumental variable model to address endogeneity, specification tests indicated that the validity of the instrument was satisfied and there was not a weak instrument problem. However, the Hausman test implied that the treatment indicator was not endogenous (P = 0.647).; CONCLUSIONS: In a managed care population with type II diabetes after adjusting for known baseline differences, the occurrence of CVD was significantly lower among subjects who augmented the short-term statin use with the statin and fibrate combination therapy compared with those who remained on the statin monotherapy. Our failure to identify “selection effects” (endogeneity issue) may be due to the strength of the instrument and the untestable assumptions.; POLICY IMPLICATIONS: People with diabetes die of CVD at rates 2-4 times higher than subjects without diabetes. Managing diabetic dyslipidemia (elevated low-density lipoprotein, decreased high-density lipoprotein, and elevated triglycerides) is regarded as one of the effective strategies to reduce the risk of CVD. We hope this result will be useful in health policy to find effective treatment strategies to reduce the risk of CVD in diabetics.

THE EFFECT OF USING FIBRATES
IN CONJUNCTION WITH STATINS FOR THE MANAGEMENT OF
DYSLIPIDEMIA IN PERSONS WITH TYPE II DIABETES MELLITUS
by
Hae Sun Suh
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(PHARMACEUTICAL ECONOMICS AND POLICY)
August 2009
Copyright 2009 Hae Sun Suh